All animal models of glaucoma have limitations. Primate physiology and anatomy most closely resemble humans, but they are not accessible to many researchers. The genetics and molecular mechanisms underlying glaucoma are studied in rodents, but the optic nerve head (ONH) is not analogous to humans. Tree shrews (Tupaia glis belangeri) are a mammalian species closely related to primates that have a robust connective tissue lamina resembling primates. The purpose of this study was to determine if sustained increases in IOP could be achieved in tree shrews after a single injection of magnetic beads, and to examine the anatomic changes that result from chronic IOP elevation using advanced imaging techniques.

Methods

Experimental glaucoma was induced in five adult tree shrews using a modified version of the bead occlusion method (Samsel et al; 2011). Briefly, magnetic beads were thoroughly washed and 0.1ml injected into the anterior chamber. Beads were directed to the angle using a magnet. IOP was measured using the iCare TonoLab tonometer weekly during the initial induction and then less frequently after the 2nd month. Throughout the study, in vivo images were obtained using Spectralis spectral domain-optical coherence tomography (SD-OCT). Circumpapillary retinal nerve fiber layer (RNFL) thickness and volume scans through the optic nerve head were obtained. At the end of the study, the eyes were fixed and three-dimensional reconstructions were created for histomorphometric analysis.

Results

In every animal, IOP in the glaucomatous eye remained significantly elevated throughout the observation period (range ~4 weeks to ~8 months) compared to the fellow control eye (32±11 vs 17±5 mmHg; p<0.001). At the end of the study, the global RNFL thickness was significantly reduced in the glaucomatous eye compared to control (61±32 vs 122±9 um; p=0.013). In vivo SD-OCT imaging showed ONH and lamina cribrosa cupping in the glaucomatous eye of all animals (Figure 1), which was confirmed by 3-D histomorphometry.

Conclusions

A tree shrew model of glaucoma has great potential as a small animal model of glaucoma that spans the gap between the rodent and nonhuman primate models. The tress shrew is less sentient than nonhuman primates, and in contrast to rodents, tree shrews have a load-bearing connective tissue lamina, more similar to primates. These initial studies provide proof of concept for further development and refinement of this model.